Neurocutaneous Melanosis in Association With Large Congenital Melanocytic Nevi in Children: A Report of 2 Cases With Clinical, Radiological, and Pathogenetic Evaluation

Abstract

Background: Melanocytic nevi present at birth, or within the first few months of life, are defined as congenital melanocytic nevi (CMN). Neurocutaneous melanosis (NCM) is a rare disorder, represents pigment cell tumors of the leptomeninges, and occurs in association with large or multiple CMN. NCM carries an extremely poor prognosis. NRAS and BRAFV600E genetic mutations were reported in CMN. Our aim was to report 2 rare cases of NCM associated with large-sized CMN.Materials and Methods: Two cases were enrolled, a 19-month-old boy with multiple satellite and giant CMN (GCMN); and a 57-month-old girl with large CMN (LCMN). Both patients had central nervous system (CNS) symptoms, and therefore, were studied from clinical, radiological, and immunohistopathological aspects. Cytogenetic study was done for one of them.Results: Both patients had CMN located in the head/neck, with no cutaneous melanoma. MRI was the most reliable method for early detection of NCM. NCM was proved in the 2 studied cases by immunohistopathology performed after surgery. The boy with GCMN carried NRAS mutation at codon 61, in addition to the characteristic facial features relevant to RASopathies. Both patients died despite surgical intervention.Conclusion: Our report highlights the need for pediatricians to be alert to the risk of NCM in association with CMN, especially when a CMN lesion is large, or there are multiple satellite lesions, or the nevus location is at the head or neck. Moreover, in the setting of CMN, the absence of skin melanoma does not exclude the presence of NCM.

Novel Finding of Copy Number Gains in GNAS and Loss of 10q in a Child With Malignant Transformation of Neurocutaneous Melanosis Syndrome

“…Moreover, the utility of chemotherapy and irradiation in the treatment of NCM is yet to be established. 7,10,11 In this report, we present a pediatric case of NCM characterized by multiple molecular aberrations including an NRAS codon 61 mutation, copy number gains of GNAS, and a loss of 10q. Both the GNAS gains and the loss of chromosome 10q have not been previously described in NCM in the current literature, but NRAS mutations are well established.…”

“…2,3,33 Unfortunately, even in patients without cutaneous or meningeal melanoma, there is still a risk of malignant transformation and/or development of neurological symptoms. 2,3,7,34,35 Once neurological symptoms develop, NCM carries a poor prognosis with limited treatment options, consisting of neurosurgical intervention to relieve elevations in intracranial pressure or mass effect on the CNS. Moreover, the utility of chemotherapy and irradiation in the treatment of NCM is yet to be established.…”

“…2,5 Various tumors, arachnoid cysts, hydrocephalus, syringomyelia, and Dandy-Walker malformation have also been associated with NCM. 4,6,7 Typically, NCM is diagnosed via magnetic resonance imaging (MRI) of the neuroaxis, along with the presence of characteristic CMN on physical examination.…”

“…2 Threeyear overall survival is poor, at , 50%, despite current treatment regimens. 4,[7][8][9] While management is not standardized, chemotherapy and irradiation have not demonstrated a survival advantage. 7,10,11 Neurosurgical tumor resections provide tissue diagnosis and prevent progressive neurologic sequelae, but are not curative.…”

“…4,[7][8][9] While management is not standardized, chemotherapy and irradiation have not demonstrated a survival advantage. 7,10,11 Neurosurgical tumor resections provide tissue diagnosis and prevent progressive neurologic sequelae, but are not curative. 9,12 More recently, molecular evaluation has demonstrated recurrent aberrations driving disease formation, including mutations in neuroblastoma RAS (NRAS) viral oncogene homolog at codon 61, as well as BRAF V600E , providing hope for the use of targeted agents in this high-risk population.…”